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Identification of the N-terminal Peptide Binding Site of Glucose-regulated Protein 94

Gidalevitz, T., Biswas, C., Ding, H., Schneidman-Duhovny, D., Wolfson, H.J., Stevens, F., Radford, S.E. and Argon, Y. (2004) Identification of the N-terminal Peptide Binding Site of Glucose-regulated Protein 94. Journal of Biological Chemistry, 279 (16). pp. 16543-16552. ISSN 1083-351X

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Because the stress protein GRP94 can augment presentation of peptides to T cells, it is important to define how it, as well as all other HSP90 family members, binds peptides. Having previously shown that the N-terminal half of GRP94 can account for the peptide binding activity of the full-length protein, we now locate this binding site by testing predictions of a molecular docking model. The best predicted site was on the opposite face of the β sheet from the pan-HSP90 radicicol-binding pocket, in close proximity to a deep hydrophobic pocket. The peptide and radicicol-binding sites are distinct, as shown by the ability of a radicicol-refractive mutant to bind peptide. When the fluorophore acrylodan is attached to Cys(117)within the hydrophobic pocket, its fluorescence is reduced upon peptide binding, consistent with proximity of the two ligands. Substitution of His(125), which contacts the bound peptide, compromises peptide-binding activity. We conclude that peptide binds to the concave face of the β sheet of the N-terminal domain, where binding is regulated during the action cycle of the chaperone.

Item Type: Article
Copyright, Publisher and Additional Information: Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
Institution: The University of Leeds
Academic Units: The University of Leeds > University of Leeds Research Centres and Institutes > Astbury Centre for Structural Molecular Biology (Leeds)
The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds)
Depositing User: Repository Officer
Date Deposited: 13 Mar 2006
Last Modified: 17 Aug 2015 21:37
Published Version: http://www.jbc.org./cgi/content/full/279/16/16543
Status: Published
Refereed: Yes
Identification Number: 10.1074/jbc.M313060200
URI: http://eprints.whiterose.ac.uk/id/eprint/607

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